Product Intro

1.Eliquis (apixaban), a direct inhibitor of factor Xa (FXa), was approved by the European Commission on May 18, 2011 for prevention of venous thromboembolic events (VTE) in adult patients who have undergone elective hip or knee replacement surgery. The discovery of apixaban was the culmination of a succession of novel and innovative medicinal chemistry discoveries starting with the identification of nonpeptide leads, rational drug design using computer-aided and X-ray crystallographic information, and the building of drug-like properties through the systematic replacement of basic groups with neutral moieties. Apixaban arose from modifications to razaxaban by constraining a pyrazole amide to form a bicyclic pyrazolo-pyridinone scaffold. Optimization of the P1 group resulted in the identification of the nonbasic methoxy phenyl group, while a P4 piperidinone improved the balance of potency and pharmacokinetics with low Vdss. The synthesis of apixaban begins with the generation of a hydrazone of 4-methoxyaniline which is then used in a 3+2 cycloaddition with a dihydropiperidinone to form a bicyclic pyrazolo-pyridinone scaffold. The distal piperidinone group is installed using an Ullmann coupling reaction followed by aminolysis of an ethyl ester on the pyrazole ring to complete the synthesis of apixaban.

2.Apixaban is an orally bioavailable, selective inhibitor of both free and prothrombinase-bound factor Xa (K_is = 0.8 nM). In vivo, apixaban has antithrombotic effects in a rabbit model of venous thrombosis. Apixaban (357.5 mg) also prevents thrombus formation without inducing adverse bleeding events in a porcine model of aortic heterotopic valve replacement. Formulations containing apixaban have been used to prevent blood clot formation in patients with atrial fibrillation.

Function

Apixaban is an oral anticoagulant with highly selective inhibition of factor Xa. It was approved by the European Medicines Agency (EMA) for the treatment of venous thromboembolic events and first marketed in Germany under the brand name Eliquis in June 2011. Apixaban was co-developed by Bristol-Myers Squibb and Pfizer and represents the first approved drug for this indication since warfarin over 50 years ago.

Application

1.Apixaban is a new form of oral anticoagulant drug developed by Bristol Myers Squibb and Pfizer. It is a new form of oral Xa factor inhibitor, and its commercial name is Eliquis. Apixaban is used to treat adult patients undergoing elective hip or knee replacement surgery to prevent venous thromboembolism (VTE).

2.Apixaban is a highly selective, reversible inhibitor of Factor Xa with Ki of 0.08 nM and 0.17 nM in human and rabbit, respectively.